This FOA issued by the National Institute of Allergy and
Infectious Diseases (NIAID), and National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK), National Institutes of Health, solicits
applications from institutions or consortia of institutions to participate in
a cooperative study group focused on prevention of human autoimmune disease.
For the purpose of this FOA, “prevention of autoimmune disease” is defined as
halting the development of an autoimmune disease prior to clinical onset by
means other than global immunosuppression. The study group has as its
foundation a set of cooperative agreements coordinated by a Steering
Committee, and also draws upon an Infrastructure and Opportunities Fund to
support a range of innovative, collaborative, and pilot/feasibility projects.

Key Dates

Posted Date

June 17, 2011

Open Date (Earliest Submission Date)

September 7, 2011

Letter of Intent Due Date

October 7, 2011

Application Due Date(s)

November 8, 2011, by 5:00 PM local time of applicant
organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March, 2012

Advisory Council Review

May, 2012

Earliest Start Date(s)

July, 2012

Expiration Date

November 9, 2011

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF
424 (R&R) Application Guide except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section
IV. When the program-specific instructions deviate from those in the
Application Guide, follow the program-specific instructions. Applications that
do not comply with these instructions may be delayed or not accepted for review.

The CSGADP [http://www3.niaid.nih.gov/about/organization/dait/CSGADP.htm]
is a unique multi-center cooperative program established in 2001 as a closely
interactive and collaborative network of investigators, with a focus on
autoimmune disease prevention and a historical emphasis on type 1 diabetes. The
Study Group has as its foundation a set of cooperative agreements coordinated
by a Steering Committee, and also draws upon an Infrastructure and
Opportunities Fund to support a range of innovative, collaborative, and pilot
and feasibility projects within and outside the Study Group membership to
further the goals of the CSGADP program. These goals include understanding the
immune mechanisms that underlie autoimmunity and autoimmune disease, the
mechanisms and consequences of manipulation of the immune response in
autoimmunity, and the application of this information to the prevention of
autoimmune diseases in humans. The purpose of this FOA is to announce continued
support for the CSGADP program for a third funding cycle; both new and renewal
applications will be accepted. The long-term goal of this program is to develop
the knowledge base necessary to design interventions for the prevention of
autoimmune disease that could be administered efficiently and safely to
individuals at risk or to the general population, including infants and
children. While such interventions might also be useful in established disease,
the focus of this program is on prevention rather than therapy. For the purpose
of this FOA, “prevention of autoimmune disease” is defined as halting the
development of an autoimmune disease prior to clinical onset by means other
than global immunosuppression.

Background

Autoimmune diseases, which disproportionately afflict women,
are debilitating, chronic illnesses that affect multiple organ systems and for
which there are currently no preventive treatments or strategies. Type 1
diabetes afflicts over 600,000 persons in the United States with peak onset in
childhood. Despite insulin treatment, long-term complications include kidney
failure, blindness, amputations, and accelerated cardiovascular disease.
Patients with type 1 diabetes are also at higher risk for celiac disease,
another autoimmune condition that causes inflammation of the digestive tract.
Multiple sclerosis afflicts over 350,000 persons in the United States; women
are affected twice as frequently as men. Although the course of the disease is
unpredictable, central and peripheral nerve impairment resulting from multiple
sclerosis can lead to blindness, weakness, loss of bowel and bladder control,
and confinement to a wheelchair. Rheumatoid arthritis, which also affects
primarily women, causes chronic pain, crippling deformity, and loss of
independence. This disease afflicts over 2 million individuals in the U.S.
population. Systemic lupus erythematosus is a multi-system autoimmune disease
that disproportionately affects African-American women and accounts for over
100,000 hospitalizations each year. Sjögren’s syndrome, which affects
predominantly middle-aged women, results in diminished lacrimal and salivary
gland function. Patients may suffer dysphagia, atrophic gastritis, esophageal
mucosal atrophy, constipation, and subclinical pancreatic insufficiency. About
30% of patients with rheumatoid arthritis, systemic lupus erythematosus and
systemic sclerosis suffer secondary Sjögren’s syndrome, while 2 to 5% of people
aged 60 and above have primary Sjögren’s syndrome. Inflammatory bowel diseases
(including Crohn’s disease and ulcerative colitis), characterized by abnormal
immune responses that result in inflammation of the intestinal lining, afflict
nearly a million persons in the United States and result in significant
morbidity including over 1 million hospital visits per year.

The 1999 Institute of Medicine report, “Vaccines for the
21st Century: A Tool for Decision Making,” concluded that the development of
antigen-specific tolerization approaches to treat or prevent type 1 diabetes,
multiple sclerosis, and rheumatoid arthritis would bring exceptionally high
economic and health benefits. The March 2005 report, “Progress in Autoimmune
Diseases Research,” [http://www3.niaid.nih.gov/healthscience/healthtopics/autoimmune/PDF/ADCCFinal.htm],
formulated by the Autoimmune Disease Coordinating Committee under the auspices
of the NIH, also emphasized the importance and great potential benefit of
research efforts aimed at prevention of autoimmune diseases, including the
development of new knowledge about underlying mechanisms of autoimmune
diseases, development of biomarkers, and effective utilization of novel
technologies and bioinformatics approaches. Subsequently, the 2007 “Evaluation
Report on the Special Statutory Funding Program for Type 1 Diabetes,” [http://www2.niddk.nih.gov/NR/rdonlyres/70F78AD8-7E2D-44BD-8812-C03731E6A9C1/0/Type_1_Diabetes_Special_Funds_Complete_ReportSept2007.pdf]
illustrated the significant progress that has been made in taking advantage of
this additional targeted funding.

A large body of evidence suggests that autoimmunity or the
autoimmune process may precede by years the development of clinical disease in
type 1 diabetes, rheumatoid arthritis, and other autoimmune diseases. Although
loss of beta cell function with development of hyperglycemia defines the
diagnosis of type 1 diabetes, evidence of autoimmunity manifested by multiple
autoantibodies to islet antigens may be detectable years earlier. In addition,
evidence of autoimmunity in healthy individuals (e.g., multiple autoantibodies
in family members of patients with type 1 diabetes who do not develop disease)
suggests that mechanisms to control autoimmunity may be operative in immune
homeostasis in healthy individuals. Similarly, in rheumatoid arthritis
development of citrullinated autoantigens, autoantibodies, and synovial cell
activation and inflammation may precede the onset of multiarticular pain and
cartilage destruction, the hallmarks of this disease. Increased understanding
of the processes for containment of autoimmunity found in healthy individuals,
identification of early markers or predictors of autoimmune processes, novel
strategies to control or prevent autoimmunity prior to the onset of clinical
disease, and safe and rational application of these strategies to humans are needed.

Since the onset of the autoimmune process may precede the
diagnosis of disease by months or years, a further understanding of neonatal
and pediatric immune homeostasis is needed, both in healthy and autoimmune
prone individuals. Intervention at the earliest possible stage may be optimal
for preventing these diseases.

Type 1 diabetes and other autoimmune diseases have been
prevented in animal models using a variety of agents hypothesized to act as
tolerogens or immunomodulators. However, our understanding of the mechanism
and consequences of these approaches in animals is incomplete. Likewise,
information on immune homeostasis of autoimmune responses in humans is
lacking. Nevertheless, the ability to selectively prevent development of or
control the activity of autoreactive cells prior to the onset of clinical
disease without impairing protective immune responses appears feasible.

Objectives
and Scope

This FOA will support a cooperative study group focused on
research for the prevention of human autoimmune disease. For the purpose of
this FOA, “prevention of autoimmune disease” is defined as halting the
development of an autoimmune disease prior to clinical onset by mechanisms
other than global immunosuppression. The Study Group will be comprised of a
consortium of investigators who, in collaboration with the NIH, will develop
and implement a Study Group Plan for autoimmune disease prevention. The Study Group
Plan will articulate the goals, specify the approaches, and define milestones
for the activities of the Study Group and will guide the Study Group Steering
Committee in the allocation of an Infrastructure and Opportunities Fund [see Section
VI.2, Cooperative Agreement Terms and Conditions of Award, "Areas of
Joint Responsibility"].

The ultimate goal of this research is to develop the
knowledge base necessary to design preventive interventions that could be administered
efficiently and safely to at-risk individuals or to the general population,
including infants and children. While the interventions may also be beneficial
in established disease, the focus of this FOA is on prevention rather than
therapy. Key accomplishments from previous funding cycles of the CSGADP include
identification of autoantigens for type 1 diabetes and potential biomarkers for
the progression of preclinical rheumatoid arthritis, elucidation of novel
mechanisms of peripheral tolerance in the setting of type 1 diabetes, and
development of microarray and nanowell technologies for probing the development
and progression of autoimmunity. In addition, the Study Group has used its
Infrastructure and Opportunities Fund to foster the development of nine
additional research projects in autoimmunity funded by NIH and private sources,
including a genome-wide scan for genes conferring susceptibility to multiple
sclerosis and grants on the homing and function of regulatory T cells in
autoimmune diseases. Although the Study Group has historically maintained a
strong interest and research program in type 1 diabetes, applications that
include projects on other autoimmune diseases or projects related to more than
one autoimmune disease are also encouraged.

Clinical studies are strongly encouraged; the use of human
samples, including specimens obtained from clinical trials, is of obvious
importance for the successful development of preventive strategies. Animal
studies proposed under this FOA should document the relevance of the model to
the development of preventive strategies for human autoimmune diseases.

Research projects should contribute knowledge critical to
achieving both of the following goals:

1. Advance the understanding of immune homeostasis in autoimmune disease states as
well as non-diseased states. This research area includes studies of the immune
control of autoantigen-specific T or B cells by mechanisms including peripheral
deletion, anergy, or control by protective or regulatory cells, as well as
research on the dysregulation of immune homeostatic mechanisms in autoimmune
diseases. Research topics include, but are not limited to:

Delineation of the phenotype and function of regulatory and effector
T cell populations in target tissues and associated lymphoid organs;

Development and regulation of the immune response to self in
healthy and autoimmune prone infants and children;

Definition of the role of the innate immune system in the maintenance
and breakdown of immune homeostasis and tolerance;

Determination of the function of antigen processing and the
activity of antigen presenting cells in the development and maintenance of self
tolerance; and

Definition of the role of genetic susceptibility and
environmental influences on loss of homeostasis in autoimmune disease.

2. Design and develop interventions to prevent human autoimmune diseases. This
includes the application of new information on the autoimmune disease process
to facilitate the design of novel approaches and the improvement of promising
strategies for autoimmune disease prevention. Research may include studies of
the feasibility and mechanisms of preventive approaches in humans. Studies of
therapeutics directed against infectious agents may be included if there is
strong evidence for a causal relationship between the infectious agent and the
occurrence of an autoimmune disease in the infected population. Research topics
include, but are not limited to:

Practical approaches to target therapeutic agents to desired
cellular populations and to evaluate their effectiveness in vivo;

Identification and testing of new adjuvants and delivery
approaches to boost regulatory cells and mechanisms;

Analyses of the consequences of intervention approaches on both
protective immunity and autoimmune responses;

Development of practical means to identify patient populations
most likely to benefit from specific interventions;

Identification, development and validation of biomarkers of
disease risk, stage, activity, and immune responses; and

Development and application of clinically relevant animal models
to facilitate the translation of preventive approaches from animals to humans.

Applicants are strongly encouraged to include studies
involving human subjects and materials as an integral part of research
projects. Examples of clinical studies that may be proposed include but not
limited to: immunological studies of patient samples obtained from ongoing or
completed clinical trials, development or validation of biomarkers of disease
risk, and comparative analyses of immune responses in diseased and non-diseased
individuals.

This FOA will not support the following:

Clinical
trials (for definitions see http://funding.niaid.nih.gov/ncn/glossary/default2.htm#clintrial).
Support for clinical trials resulting from research supported by the Study
Group may be sought through arrangements with other programs, including but not
limited to the Autoimmunity Centers of Excellence, the Immune Tolerance
Network, or the Type 1 Diabetes TrialNet program.

Specifically
excluded from the scope are studies of globally
immunosuppressive therapies. This is in keeping with the above definition of
“prevention of autoimmune disease” which, for the purposes of this FOA,
specifically excludes global (general or non-specific) immunosuppression as a
means of halting the development of autoimmune disease.

Applications proposing above studies will be considered
non-responsive and will not be reviewed.

Steering
Committee

A Steering Committee will be established to direct the
overall efforts of the Study Group, approve uses of the Infrastructure and
Opportunities Fund, and evaluate the progress and direction of Study Group
investigators. Steering Committee responsibilities are described further under Section VI.2, Cooperative Agreement Terms
and Conditions of Award, "Areas of Joint Responsibility."

Infrastructure
and Opportunities Fund

An Infrastructure and Opportunities Fund (IOF) will be made
available after award to support Study Group activities and collaborative
projects consistent with the goals of this program. The IOF may also be used to
support new research opportunities not proposed at the time of award, including
pilot projects proposed by Study Group members or other investigators, and
development of reagents and resources in furtherance of the Study Group's
mission.

After all Study Group awards have been issued, one or more
awardee institutions will be selected by NIAID to administer the IOF. Applications
from institutions with an interest in administering the IOF should include a
letter of support from the business office as detailed in Section IV.2,
Research Plan Component. All applicants shall submit budgets that reflect
solely the needs of their individual applications and shall not include budgets
for administration of the IOF. The IOF is described further under Section VI.2, Cooperative Agreement Terms
and Conditions of Award, "Areas of Joint Responsibility."

Section
II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there
will be substantial Federal scientific or programmatic involvement.
Substantial involvement means that, after award, scientific or program staff
will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Renewal

The OER
Glossary and the SF 424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH
appropriations, and the submission of a sufficient number of meritorious
applications.

NIAID and NIDDK intend to fund approximately 5-6 U01
awards, corresponding to a total of $2.6 million, plus an Infrastructure and
Opportunities Fund, for fiscal year 2012. Future year amounts will depend on
annual appropriations.

Award Budget

Application budgets are not limited, but need to reflect
actual needs of the proposed project. Because the nature and scope of the
proposed research will vary from application to application, it is
anticipated that the size of each award will also vary. In previous years of
this program the average amount of funding for each project within a U01 grant
has been $200,000 to $250,000 annual direct costs. Applicants may have valid
reasons for deviating from this range, and are encouraged to discuss such
deviations with the Scientific/Research Contact listed in Section VII below.

Award Project Period

In the interest of group cohesion, applicants should
request and plan for a project period of five years.

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions:

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Directors/Principal Investigators (PD/PIs) must
also work with their institutional officials to register with the eRA Commons
or ensure their existing eRA Commons account is affiliated with the eRA Commons
account of the applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director/Principal
Investigator (PD/PI) is invited to work with his/her organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed.

Section
IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and
Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding opportunity
announcement to do otherwise. Conformance to the requirements in the
Application Guide is required and strictly enforced. Applications that are out
of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The forms package associated with this FOA includes all
applicable components, mandatory and optional. Please note that some
components marked optional in the application package are required for
application submission. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Letters of Support

Letter
of Institutional Support for the IOF Administration Plan (optional)

Applications from institutions with an interest in
administering the IOF should include a letter of support from the institutional
business office detailing their plans for IOF administration. An institution
chosen by NIAID to administer the IOF must agree to take responsibility for
managing the IOF as directed by the Steering Committee. Projects approved by
the Steering Committee for IOF support will be funded as subcontracts under the
CSGADP grant to the institution managing the IOF, and thus generate the same
additional responsibilities as any subcontract. The responsibilities of the IOF
will include disbursement and tracking of funds, ensuring regulatory compliance
by subcontractors (e.g. IACUC approvals, human subjects reporting), and
collection of materials for inclusion in the parent grant's annual progress
reports.

For planning purposes, applicants may assume that
twelve IOF subcontracts will be issued each fiscal year, with an average cost
of $100,000 and a typical duration of one year.

Prior to award, the site selected to administer the
IOF will be asked to submit a budget for the costs of administration, with the
final level of support to be negotiated with NIAID. Support for administrative
costs may be allocated from the IOF.

Budget note: All PD/PIs will be
required to attend an annual Study Group meeting, either in the Washington, DC
area or at one of the member sites. The cost of this travel should be included
in each individual project’s budget.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested
for any one year, should address a Data Sharing Plan.

Appendix

Do not use the appendix to circumvent page limits. Follow
all instructions for the Appendix as described in the SF424 (R&R)
Application Guide.

Foreign Organizations

Foreign (non-US) organizations must follow policies
described in the NIH Grants
Policy Statement, and procedures for foreign organizations described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in
advance of the deadline to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants
are responsible for viewing their application in the eRA Commons to ensure accurate
and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

Expenditure of any Infrastructure and Opportunity Funds
allocated to the Study Group under this FOA will be restricted to projects
approved by the Steering Committee as meritorious and consistent with the goals
of this program and the guidelines of the Study Group Plan.

6. Other Submission Requirements and
Information

Applications must be submitted electronically following the
instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD/PIs must include their eRA Commons ID in the Credential
fieldof the Senior/Key Person Profile Component of the SF 424(R&R) Application
Package. Failure to register in the Commons and to include a valid PD/PI
Commons ID in the credential field will prevent the successful submission of an
electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the Central Contractor Registration (CCR). Additional information
may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by NIAID, NIH. Applications that are
incomplete and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section
V. Application Review Information

1. Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in
consideration of the following review criteria and additional review criteria
(as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field? Does the
proposed research project contribute knowledge critical to advancing the
understanding of immune homeostasis in autoimmune disease states as well as
non-diseased states? Does the proposed research project contribute knowledge
critical to the design and development of interventions to prevent human autoimmune
diseases?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers
well suited to the project? If Early Stage Investigators or New Investigators,
or in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

For Renewals, the committee will consider the
progress made in the last funding period.

Revisions

Not Applicable.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by NIAID, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review), will be discussed and assigned an overall impact/priority
score.

Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications
will receive a second level of review by the appropriate Advisory Council l. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities. This may include representation of a programmatically appropriate spectrum of autoimmune
diseases and/or approaches.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant
administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable
when State and local Governments are eligible to apply), and other HHS, PHS,
and NIH grant administration policies.

The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.

The
PD(s)/PI(s)will have the primary responsibility for all
aspects of the proposed studies. In addition:

All investigators funded under this FOA, including recipients of IOF
awards, are required to accept and implement policies and activities approved
by the Steering Committee, including participation in an annual meeting of all
investigators funded under this FOA.

Publications and oral presentations of work performed under this
agreement will require appropriate acknowledgment of support by the Cooperative
Study Group for Autoimmune Disease Prevention and the appropriate funding
agency and grant number. Early publication of major findings is encouraged.
Publication of findings linked to clinical trials (for example, mechanistic
studies that utilize samples from a clinical trial) must adhere to the policies
enacted by the governing body of the clinical trial and the sponsor of the
trial.

Awardees will retain custody of and have primary rights to the
data and software developed under these awards, subject to Government rights of
access consistent with current DHHS, PHS, and NIH policies.

NIH
staffhave substantial programmatic involvement that is
above and beyond the normal stewardship role in awards, as described below:

NIAID staff assistance will be provided by a Program
Official from the Clinical Immunology Branch, Division of Allergy, Immunology
and Transplantation, NIAID, or his/her designee, who will serve as the NIAID
Project Scientist. During the performance of this award, the NIAID Project
Scientist, with assistance from other scientific program staff who are
designated based on the research topic and their relevant expertise, may
provide appropriate assistance, advice, and guidance by:

participating in the design of the activities of the Study Group;

advising in the selection of sources or resources;

advising in project management and technical performance;

serving as liaison to other autoimmunity-related NIH programs
including the Immune Tolerance Network, the Autoimmunity Centers of Excellence,
and the Type 1 Diabetes TrialNet;

recruiting external advisors to the Study Group from the
international autoimmunity research community and soliciting their advice and
attendance at Study Group meetings; and

participating in the preparation of publications for
collaborative projects, as appropriate.

However, the role of the NIAID Project Scientist will be to
facilitate, and not to direct, the activities of the Study Group. The Project
Scientist and other funding agency staff will participate in Steering Committee
discussions as an integral part of the committee's decision-making process,
with the goal of achieving consensus-based progress toward the goals elucidated
in the Study Group Plan. Additionally, an agency program official or IC program
director will be responsible for the normal scientific and programmatic
stewardship of the award and will be named in the award notice.

Areas
of Joint Responsibility include:

Steering Committee

A Steering Committee will serve as the governing body of the
Study Group and will be responsible for development and implementation of the
Study Group Plan (see below). At a minimum, the Steering Committee will be
composed of the Program Directors/Principal Investigators of each of the
awarded grants, and the NIH Project Scientist serving as a representative of
the funding ICs. The Steering Committee or the NIH may identify and appoint
other members, as appropriate. A Chairperson will be selected by the Steering
Committee from among the non-federal Committee members for an initial term of
one year. The Steering Committee will meet at least twice in the first year and
at least annually thereafter, and will reappoint the existing Chairperson or
select a new Chairperson at each annual meeting. Subcommittees of the Steering
Committee may be established as necessary. The NIAID Project Scientist will
schedule the meetings of the Steering Committee and actively assist the
Chairperson in developing the meeting agendas. Each Steering Committee member
will be expected to participate in all meetings and other Steering Committee
activities, such as conference calls and subcommittee meetings, as may be
necessary to accomplish the work of the Study Group.

The Steering Committee will also be responsible for ensuring that
the activities of all Study Group members are coordinated, productive,
collaborative when appropriate, and directed toward the goals expressed in the
Study Group Plan and the overall goal of developing preventive strategies for
human autoimmune diseases. The Steering Committee will convene meetings of all
investigators (PIs of U01 awards and all investigators funded by the IOF) to
facilitate review of the progress of all projects on an annual basis. The
funding agencies may also invite external experts to attend these meetings for
the purpose of providing additional advice to the Steering Committee and
funding agencies. The Steering Committee will make recommendations to the NIAID
Project Scientist for continuation or redirection of ongoing projects,
incorporation of additional expertise or resources needed for accomplishing
project or program goals, and extensions and modifications to the Study Group
Plan.

The Steering Committee will have access to an Infrastructure and
Opportunities Fund (IOF) to support:

Study Group activities and collaborative projects consistent with
the goals of this program and the Study Group Plan;

innovative pilot and feasibility projects; and

development of reagents and resources, including shared
resources, required to accomplish the goals expressed in the Study Group Plan.

The Steering Committee’s responsibility to conduct and oversee
these activities is intended to encourage those cooperative and collaborative
efforts, among Study Group members and the research community at large, that
are best suited to achieve the goals of the program and to advance the field of
autoimmune disease prevention. As part of this effort, the Steering Committee
will devise and implement means to make the autoimmunity research community
aware of the Study Group’s IOF project program and to ensure appropriate
participation by researchers outside the Study Group. This will include
establishment, with concurrence of the NIAID Project Scientist, of guidelines
and procedures for solicitation and review of applications, funding levels, and
monitoring progress of projects.

Study
Group Plan

The Steering Committee will be responsible for development of the
Study Group Plan, which will articulate the goals, specify the approaches, and
define milestones for the activities of the Study Group. The purpose of the
Study Group Plan is to set an overall agenda for the Study Group’s activities
designed to produce maximum progress in the field of autoimmune disease
prevention. It is anticipated that development of an optimal plan will involve
consultation with external advisors from the international autoimmunity
research community, as facilitated by the NIAID Project Scientist. The initial
Study Group Plan will outline critical areas to be addressed through
collaborative, coordinated, and/or pilot projects as described above, and will
be submitted to the NIAID Program Officer within six months of the initial
award. As part of the Steering Committee’s annual review of all Study Group
projects and activities, the Study Group Plan will also be reviewed and
modified as necessary to address new opportunities and problems in the field.

Dispute
Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
composed of three members will be convened. It will have three members: a
designee of the Steering Committee chosen without NIH staff voting, one NIH
designee, and a third designee with expertise in the relevant area who is
chosen by the other two; in the case of individual disagreement, the first
member may be chosen by the individual awardee. This special dispute resolution
procedure does not alter the awardee's right to appeal an adverse action that
is otherwise appealable in accordance with PHS regulation 42 CFR Part 50,
Subpart D and DHHS regulation 45 CFR Part 16.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award as described in the NIH Grants Policy
Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.